tbuckley/cabot-search huggingface dataset:
Abstract 5525: Community cancer research advocates: Helping underrepresented minority groups become research ready
Authors: Sarah Been, Susan Gertz, Susan Hershberger, Melinda Butsch Kovacic
Journal: Cancer Research (2023)

Abstract Even though certain racial/ethnic minority groups get cancer more often, are diagnosed at younger ages, and are at risk for earlier death, clinical trials fail to include adequate proportions of representatives from these groups. Encouraging equitable participation in research becomes an important tool in the fight against cancer disparities. Therefore, we co-created with community representatives a graphic-style story entitled “Research Ready” that is used by trained Community Research Advocates (including some survivors or family of survivors themselves) to hold brief discussions to help eligible hesitant participants to learn the 3 P’s: the purpose of cancer research, how they are kept safe while participating, and why people from diverse backgrounds are needed to participate. Importantly, advocates use a Research Review activity to discuss factors that influence their willingness to participate as well as identify questions they have for the research study’s staff. Focus group and survey-based evaluation data show these discussions to be useful in increasing hesitant patients’ willingness to consider participation in research and increase perception of safety. Advocates too appreciate the opportunity to serve. While this pilot is small, additional partnerships within the University of Cincinnati Cancer Center to expand the program will be developed. Future partnership with a community patient navigator program will also enable additional support and transportation to research appointments. Collectively, we anticipate that this program will ultimately support hesitant patients’ decision-making and improve cancer research participation particularly among racial/ethnic minorities. Citation Format: Sarah Been, Susan Gertz, Susan Hershberger, Melinda Butsch Kovacic, We Engage 4 Health Community-Academic Partnership. Community cancer research advocates: Helping underrepresented minority groups become research ready. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5525.
Abstract 1720: Examining mechanistic underpinnings of chemoresistance in triple negative breast cancer
Authors: Qitong Wu, Sumit Siddharth, Deepak Verma, Sheetal Parida, Dipali Sharma
Journal: Cancer Research (2023)

Abstract Background: Triple negative breast cancer (TNBC) is not only the most aggressive subtype of breast cancer, but it does also not have many targeted therapeutic options due to the lack of hormone receptor expression and enrichment of HER2. TNBCs are also more prone to the development of chemoresistance and metastatic progression, which are the main obstacles to reducing TNBC-related mortality. The objective of this study is to identify targetable key node (s) that contribute to the development of chemoresistance in TNBC. Method: Differentially expressed genes in TNBC patients with or without relapse were analyzed to select functionally important genes in chemoresistant TNBC. TRIM29 was selected based on survival analysis. Carboplatin-resistant TNBC cells were established to explore the phenotypic and molecular differences. Various growth and migration assays were used to explore the phenotype of chemoresistant TNBC cells. The expression of TRIM29 and related pathways were assessed by immunoblotting and immunofluorescence analysis. Cells with TRIM29-knockout (KO) were developed by the CRISPR system. Result: Chemoresistant TNBC cells overexpress TRIM29. Exhibiting the functional importance, overexpression of TRIM29 in MDAMB231 confers resistance to carboplatin. A stable knockout of TRIM29 in carboplatin-resistant cells results in an improved response to carboplatin. The breast tumor xenograft model revealed that TRIM29-KO in chemoresistant TNBC formed significantly less dense tumor in mice compared to control. Mechanistically, an enhanced expression of β-catenin was seen in chemoresistant as well as TRIM29-overexpressing cells. TRIM29-KO in carboplatin-resistant cell line results in a drastic decrease in β-catenin level. Combination treatment of carboplatin and β-catenin-inhibitor resulted in an enhanced growth inhibition in chemoresistant TNBC cells. RNA-Seq analysis revealed that there are 24 candidate genes which are overexpressed in chemoresistant TNBC cells but downregulated in TRIM29-KO chemoresistant cells, thereby demanding further investigation. Conclusion: Our findings implicate TRIM29 enrichment as an important node in chemoresistant TNBC that may concomitantly modulate β-catenin as downstream oncogenic effectors. Citation Format: Qitong Wu, Sumit Siddharth, Deepak Verma, Sheetal Parida, Dipali Sharma. Examining mechanistic underpinnings of chemoresistance in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1720.
Abstract 5503: Targeting CDK12-mediated DNA damage response to overcome cisplatin resistance in human urothelial carcinoma
Authors: Po-Ming Chow, Jun-Ren Dong, Chung-Sheng Shi, Kuo-How Huang
Journal: Cancer Research (2023)

Abstract Urothelial carcinoma (UC) accounts for more than 90% of bladder cancer. According to the 2019 Surveillance, Epidemiology and End Results (SEER) Program database, the 5-year survival rates of regional and metastatic bladder cancer are 36.3% and 4.6%, respectively. Patients who received radical cystectomy suffer from a high recurrence rate of up to 30%. As for metastatic UC, only half of the patients respond to standard platinum-based chemotherapy, with 20% of 5-year overall survival. CDK12 shows transcription regulatory effects via regulating RNA polymerase II CTD phosphorylation. In our research, we used CDK12 selective inhibitor SR-4835 to treat the UC cell lines including T24, BFTC905, RT4, and cisplatin-resistant T24/R. MTT assay result has demonstrated the cytotoxicity of SR-4835 against UC cells. Using q-RT-PCR and immunoblotting, we have confirmed the reduction of ATM mRNA and protein expression after the treatment of SR-4835. The expression of DNA damage marker gamma-H2AX was also elevated. Flow cytometry data indicated an increase in apoptotic population after treatment. According to these findings, we presume SR-4835 can lead to a DNA damage-induced apoptosis process. Furthermore, we also observed the inhibition of AKT pathway, which is related to cell survival and proliferation. Due to the effects of DNA-repair inhibition, we aim to combine SR-4835 to enhance the anti-cancer effects of cisplatin. The results of UC mice xenograft have confirmed that SR-4835 and cisplatin display a synergistic effect against UC tumor growth in vivo. We will further dissect the mechanisms of the in vitro synergistic effects between SR-4835 and cisplatin using immunoblotting, RNA-sequencing, comet assay, and various functional assays. Conclusively, our study aims to explore the role of CDK12 in urothelial carcinoma and the therapeutic effects of SR-4835, especially its potential to overcome cisplatin resistance and manage metastatic disease. Citation Format: Po-Ming Chow, Jun-Ren Dong, Chung-Sheng Shi, Kuo-How Huang. Targeting CDK12-mediated DNA damage response to overcome cisplatin resistance in human urothelial carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5503.
Abstract 6290: Characterizing antitumor responses to EXS-74539, a novel, reversible LSD1 inhibitor with potential in small-cell lung cancer
Authors: Andrew Payne, Manisha Naik, Simon Richards, Victor Sebastian Perez, Maria Dominguez
Journal: Cancer Research (2023)

Abstract Background: Lysine demethylase 1 (LSD1) is a potentially important target in oncology due to its role in demethylating histones and suppressing expression of genes required for cellular differentiation. In small-cell lung cancer (SCLC), high LSD1 expression is associated with suppressed differentiation pathways. Although selective LSD1 compounds are in clinical development, understanding of the molecular markers of tumor sensitivity to inhibition of LSD1 inhibition is incomplete. Methods: We report on the pharmacological characterization of EXS-74539, a potent, selective and reversible LSD1 inhibitor. We assessed EXS-74539 efficacy in in vitro and in vivo SCLC cell line models, encompassing the four molecular subtypes of SCLC tumor cells previously proposed (Rudin et al, 2019), based on differential expression of key transcription regulators, ASCL1, NEUROD1, POU2F3 and YAP1. Results: In vitro, EXS-74539 demonstrated similar anti-proliferative activity against both neuroendocrine (NCI-H1417 and NCI-H69, ASCL1 sub-type) and non-neuroendocrine (NCI-H526: POU2F3) SCLC cell lines, with IC50 values of 28, 12 and 11 nM, respectively. In vitro exposure of these cell lines to EXS-74539 led to concentration-dependent alterations in differentiation-associated genes. However, in vivo, significant differences in antitumor growth response upon LSD1 inhibition were observed between the cell lines; NCI-H69 tumor growth was unaffected following treatment with EXS-74539 and an irreversible LSD1 inhibitor at dose regimens which were efficacious in the NCI-H1417 and NCI-H5126 models. We describe in vitro and in vivo gene expression correlations associated with LSD1 sensitivity. Conclusions: The reversible LSD1 inhibitor, EXS-74539, is a potent inhibitor of SCLC cell line proliferation and shows in vivo efficacy. Characterizing SCLC cell line sensitivity in vitro and in vivo identified gene signatures that may have use as markers of sensitivity, which we are currently characterizing and validating in human SCLC patient samples. Rudin et al., Nat Rev Cancer, 2019 Citation Format: Andrew Payne, Manisha Naik, Simon Richards, Victor Sebastian Perez, Maria Dominguez. Characterizing antitumor responses to EXS-74539, a novel, reversible LSD1 inhibitor with potential in small-cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6290.
Abstract 3622: Characterizing the metastatic potential and clonal dynamics of invasive subpopulations in TNBC cells in response to chemotherapy
Authors: Carolina De Santiago, Amy Brock
Journal: Cancer Research (2023)

Abstract Triple negative breast cancer (TNBC) is one of the deadliest forms of breast cancer and is characterized by its high rates of metastasis, significant intra-tumor heterogeneity and lack of hormonal treatments. Through utilization of a novel genetic cell tracking technology, ClonMapper, we identify and characterize the origins of invasive subpopulations. Genetic barcodes are stably integrated into HCC1806 cells to generate starting parental populations of ~1000 unique barcoded cells. Invasive barcoded subpopulations were selected by migration through transwell assays for 24 hours and then collected for expansion. Clonal abundance sequencing across all replicates showed a &amp;gt;8-fold decrease in the number of unique barcodes. Similarity was quantified using the Bray-Curtis and Cosine similarity indexes. 5 out of 8 replicates shared the same lineages, where more than 50% of the replicates were composed of the same 9 unique barcodes thus indicating the pre-existence of invasive clones. Following cell subpopulation isolation, we observed that isolated subpopulations display faster growth rates than parental populations. A scratch assay verified that the 5 similar invasive subpopulations displayed elevated migration rates in this 2D migration format (invasive populations vs parental population, n= 6). Separate transwell assays also confirmed the 3-dimensional migration rates of isolated subpopulations. Parental HCC1806 and invasive subpopulations were treated with doxorubicin, cisplatin, paclitaxel and 5-flourouracil (5-FU) at their respective LD50 for 48 hours then allowed to recover to confluency before assessment by scratch assay. We observed that paclitaxel significantly decreased the migration rate, but that both doxorubicin and 5-FU resistant cells had a significantly higher migration rate (chemoresistant populations vs parental population, n=5) indicating that these drugs select for more migratory populations. Future studies will elucidate whether invasive clones are pre-existing or de novo and determine the effect of chemotherapeutics on these populations. Citation Format: Carolina De Santiago, Amy Brock. Characterizing the metastatic potential and clonal dynamics of invasive subpopulations in TNBC cells in response to chemotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3622.
Abstract 3809: Differential regulation of novel long non coding RNAs and their mechanism of action in p73 dependent manner
Authors: Chanchal Bareja, Apoorva Uboveja, Daman Saluja
Journal: Cancer Research (2023)

Abstract The p53 tumor suppressor family is classically activated after DNA damage and plays a central role in cell fate decisions. Although, the p53 family activates many of the same genes in response to DNA damage, p73 plays distinct biological functions in development and metastasis. It is likely that p73 activates a unique transcriptional network which is critical for its anti-metastatic and anti-invasive action. Long non-coding RNAs (lncRNAs) are a class of mRNA- like transcripts longer than 200 nucleotides. They lack protein-coding ability and are believed to be involved in various kinds of biological processes. Increasing evidence suggests that lncRNA are frequently aberrantly expressed in cancers. Therefore, the roles of dysregulated functional lncRNA in human malignant tumors have attracted considerable scientific interest. The objective of our study is to find out novel long non-coding RNAs that can act as transcriptional targets of p73 and to delineate their role in p73-mediated anti-metastatic response. For this purpose, we performed transcriptome sequencing in HCT116p73wt and HCT116p73KD cells and screened the data for modulation of expression of lncRNAs in differential manner. Quantitative Real Time PCR was further carried out to validate the data obtained after screening RNA seq Data. Promoter analysis was carried out for the identification of p73 binding sites in the selected upregulated or downregulated lncRNAs which was further confirmed by Luciferase reporter, ChIP and site directed mutagenesis assays. About six lncRNAs were observed to be significantly upregulated while four were down-regulated upon knockdown of p73. The promoters of selected lncRNAs were analysed in silico using TF Bind and JASPAR software for p73 binding sites and luciferase reporter assays suggested regulation of lncRNAs by p73. Chromatin immunoprecipitation showed promoter enrichment of the selected lncRNAs. Together, our study provides insights into the differential regulation of long non- coding RNAs in p73 dependent manner which further will provide the mechanism of their action at the genome level. Citation Format: Chanchal Bareja, Apoorva Uboveja, Daman Saluja. Differential regulation of novel long non coding RNAs and their mechanism of action in p73 dependent manner. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3809.
Effect of 12 Months of Whole-Body Vibration Therapy on Bone Density and Structure in Postmenopausal Women
Authors: Lubomira Slatkovska, Shabbir M.H. Alibhai, Joseph Beyene, Hanxian Hu, Alice Demaras, Angela M. Cheung
Journal: Annals of Internal Medicine (2011)

Background: Although data from studies in animals demonstrated beneficial effects of whole-body vibration (WBV) therapy on bone, clinical trials in postmenopausal women showed conflicting results. Objective: To determine whether WBV improves bone density and structure. Design: A 12-month, single-center, superiority, randomized, controlled trial with 3 parallel groups. (ClinicalTrials.gov registration number: NCT00420940) Setting: Toronto General Hospital, Ontario, Canada. Participants: 202 healthy postmenopausal women with bone mineral density (BMD) T-scores between −1.0 and −2.5 who were not receiving prescription bone medications. Intervention: Participants were randomly assigned to 1 of 3 groups (1:1:1 ratio) by using a block-randomization scheme and sealed envelopes. They were asked to stand on a low-magnitude (0.3g) 90-Hz or 30-Hz WBV platform for 20 minutes daily or to serve as control participants; all participants received calcium and vitamin D. Measurements: Bone outcome assessors, who were blinded to group assignment, determined trabecular volumetric BMD and other measurements of the distal tibia and distal radius with high-resolution peripheral quantitative computed tomography and areal BMD with dual-energy x-ray absorptiometry at baseline and at 12 months. Results: 12 months of WBV therapy had no significant effect on any bone outcomes compared with no WBV therapy. For the primary outcome of tibial trabecular volumetric BMD, mean change from baseline was 0.4 mg/cm3 (95% CI, −0.4 to 1.2 mg/cm3) in the 90-Hz WBV group, −0.1 mg/cm3 (CI, −1.0 to 0.8 mg/cm3) in the 30-Hz WBV group, and −0.2 mg/cm3 (CI, −1.1 to 0.6 mg/cm3) in the control group (P = 0.55). Changes in areal BMD at the femoral neck, total hip, and lumbar spine were also similar among the groups. Overall, low-magnitude WBV at both 90 and 30 Hz was well-tolerated. Limitations: Adherence to WBV ranged from 65% to 79%. Double-blinding was not possible. Conclusion: Whole-body vibration therapy at 0.3g and 90 or 30 Hz for 12 months did not alter BMD or bone structure in postmenopausal women who received calcium and vitamin D supplementation. Primary Funding Source: Physicians' Services Incorporated Foundation.
Causal evidence for the processing of bodily self in the anterior precuneus
Authors: Dian Lyu, James Robert Stieger, Cindy Xin, Eileen Ma, Zoe Lusk, Mariel Kalkach Aparicio, Katherine Werbaneth, Claire Megan Perry, Karl Deisseroth, Vivek Buch, Josef Parvizi
Journal: Neuron (2023)
Circular RNAs drive oncogenic chromosomal translocations within the MLL recombinome in leukemia
Authors: Vanessa M. Conn, Marta Gabryelska, John Toubia, Kirsty Kirk, Laura Gantley, Jason A. Powell, Gökhan Cildir, Shashikanth Marri, Ryan Liu, Brett W. Stringer, Scott Townley, Stuart T. Webb, He Lin, Saumya E. Samaraweera, Sheree Bailey, Andrew S. Moore, Mellissa Maybury, Dawei Liu, Alex D. Colella, Timothy Chataway, Craig T. Wallington-Gates, Lucie Walters, Jane Sibbons, Luke A. Selth, Vinay Tergaonkar, Richard J. D’Andrea, Stuart M. Pitson, Gregory J. Goodall, Simon J. Conn
Journal: Cancer Cell (2023)
Detection of mpox using polymerase chain reaction from the skin and oropharynx over the course of infection: A prospective study
Authors: Catarina Correia, Miguel Alpalhão, Diogo de Sousa, Joana Vieitez-Frade, Ana Pelerito, Rita Cordeiro, Isabel Lopes de Carvalho, Maria Sofia Núncio, João Ferreira, Paulo Filipe
Journal: Journal of the American Academy of Dermatology (2023)
Signaling pathways and intervention for therapy of type 2 diabetes mellitus
Authors: Rong Cao, Huimin Tian, Yu Zhang, Geng Liu, Haixia Xu, Guocheng Rao, Yan Tian, Xianghui Fu
Journal: MedComm (2023)

Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for a broad range of comorbidities, including vascular, visual, neurological, kidney, and liver diseases. Moreover, recent data suggest a mutual interplay between T2DM and Corona Virus Disease 2019 (COVID-19). T2DM is characterized by insulin resistance (IR) and pancreatic β cell dysfunction. Pioneering discoveries throughout the past few decades have established notable links between signaling pathways and T2DM pathogenesis and therapy. Importantly, a number of signaling pathways substantially control the advancement of core pathological changes in T2DM, including IR and β cell dysfunction, as well as additional pathogenic disturbances. Accordingly, an improved understanding of these signaling pathways sheds light on tractable targets and strategies for developing and repurposing critical therapies to treat T2DM and its complications. In this review, we provide a brief overview of the history of T2DM and signaling pathways, and offer a systematic update on the role and mechanism of key signaling pathways underlying the onset, development, and progression of T2DM. In this content, we also summarize current therapeutic drugs/agents associated with signaling pathways for the treatment of T2DM and its complications, and discuss some implications and directions to the future of this field.
Optimal transplantation strategy using human induced pluripotent stem cell‐derived cardiomyocytes for acute myocardial infarction in nonhuman primates
Authors: Hong‐mei Li, Ting Wang, Yu‐yin Feng, Ke Sun, Guang‐rui Huang, Yu‐lin Cao, An‐long Xu
Journal: MedComm (2023)

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have the potential to be a therapeutic option for myocardium restoration. However, hiPSC-CMs of varying maturation and transplantation routes exhibit different reactivity and therapeutic effects. We previously demonstrated that the saponin
Mouse frontal cortex mediates additive multisensory decisions
Authors: Philip Coen, Timothy P.H. Sit, Miles J. Wells, Matteo Carandini, Kenneth D. Harris
Journal: Neuron (2023)

The brain can combine auditory and visual information to localize objects. However, the cortical substrates underlying audiovisual integration remain uncertain. Here, we show that mouse frontal cortex combines auditory and visual evidence; that this combination is additive, mirroring behavior; and that it evolves with learning. We trained mice in an audiovisual localization task. Inactivating frontal cortex impaired responses to either sensory modality, while inactivating visual or parietal cortex affected only visual stimuli. Recordings from >14,000 neurons indicated that after task learning, activity in the anterior part of frontal area MOs (secondary motor cortex) additively encodes visual and auditory signals, consistent with the mice's behavioral strategy. An accumulator model applied to these sensory representations reproduced the observed choices and reaction times. These results suggest that frontal cortex adapts through learning to combine evidence across sensory cortices, providing a signal that is transformed into a binary decision by a downstream accumulator.